Throughout this application various publications are referenced, many in parenthesis. Full citations for these publications are provided at the end of the Detailed Description of the Invention. The disclosures of these publications in their entireties are hereby incorporated by reference in this application.
Two novel DNA fragments belonging to a previously unidentified human herpesvirus were recently identified in a Kaposi's sarcoma (KS) lesion (Chang et al. 1994). Extensive sequencing, transmission and serologic studies demonstrate that these sequences belong to a new human herpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV), also called human herpesvirus 8 (HHV 8) (Moore et al. 1996a). While this virus is generally absent from normal control tissues, it is consistently present in AIDS- and non-AIDS-related KS (Boshoff et al. 1995; Chang et al. 1994; Chang et al. 1996; Dupin et al. 1995b; Moore and Chang 1995; Schalling et al. 1995), AIDS- and non-AIDS-related primary effusion (body cavity-based) lymphomas (Cesarman et al. 1995a; Karcher and Alkan 1995), and a significant proportion of cases of multicentric Castleman's disease (Dupin et al. 1995a; Gessain et al. 1995; Soulier et al. 1995). These sequences are also frequently present in normal appearing tissue adjacent to KS lesions, and in lymph nodes and peripheral blood B cells in patients with KS or at high risk for developing KS (Ambroziak et al. 1995; Chang et al. 1994; Moore et al. 1996b; Noel 1995; Shigandia et al. 1995; Whitby et al. 1995).
Detection of KSHV in lymph nodes, peripheral blood B-cells, and a subset of B-cell lymphomas suggests that it is a lymphotropic herpesvirus. The initial sequence analysis data showing partial homology to Herpesvirus saimiri (HVS) and Epstein-Barr virus (EBV) is consistent with this hypothesis (Chang et al. 1994). Both viruses are members of the Gammaherpesvirinae subfamily of herpesviruses, which characteristically replicate in lymphoblastoid cells. HVS, a squirrel monkey virus (Saimiri scireus), can be isolated from the peripheral blood mononuclear cells of healthy animals, but causes fulminant T-cell lymphomas in New World primates other than its natural hosts (Fleckenstein and Desrosiers 1982). HVS can also immortalize human T cells so that they grow continuously in vitro (Biesinger et al. 1992). EBV is a human herpesvirus well known to immortalize B cells in vitro and is associated with malignant lymphomas, including endemic Burkitt's lymphoma, AIDS-related lymphomas, post-transplantation lymphoproliferative disorders, and Hodgkin's disease (Miller 1990). Since both viruses can lead to the development of malignant lymphomas, it is quite possible that KSHV is a transforming virus which is involved in the development of primary effusion lymphomas.
Since the original identification of two small DNA fragments from an AIDS-KS lesion by representational difference analysis, considerable progress has been made in determining the nature of this virus. Cell lines have been established which allow the in vitro culture of the virus and detailed virologic characterization studies (Arvanitakis et al. 1996; Cesarman et al. 1995b). A 20.7 kb clone from a KS library has been sequenced and characterized, confirming that KSHV is a gamma-2 herpesvirus, the first member of the genus Rhadinovirus known to infect humans (Moore et al. 1996a). In vitro transmission and visualization at the electron microscopic level have also been achieved, providing additional evidence for the viral nature of the KSHV sequences (Mesri et al. 1996; Moore et al. 1996a; Renne et al. 1996; Said et al. 1996).
A need continues to exist for more information about KSHV, including the identification and/or sequencing of proteins of this virus. Such proteins, when identified and sequenced, could be used in many ways.